Exploring Hematoma Expansion Shift With Recombinant Factor VIIa: A Pooled Analysis of 4 Randomized Controlled Trials

Authors

Vignan Yogendrakumar, Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia (V.Y.).
Stephan A. Mayer, Departments of Neurology and Neurosurgery, New York Medical College, Valhalla, NY (S.A.M.).
Thorsten Steiner, Department of Neurology, Klinikum Frankfurt Höchst, Germany (T.H.).
Joseph P. Broderick, University of Cincinnati Gardner Neuroscience Institute, OH (J.P.B.).
Dar Dowlatshahi, Department of Medicine (Neurology), University of Ottawa and Ottawa Hospital Research Institute, Ontario, Canada (D.D.).

Author Type(s)

Faculty

Journal Title

Stroke

First Page

2990

Last Page

2998

Document Type

Article

Publication Date

12-1-2023

Department

Neurology

Abstract

BACKGROUND: Hematoma expansion shift (HES) analysis can be used to assess the biological effect of a hemostatic therapy for intracerebral hemorrhage. In this study, we applied HES analysis to individual patient data from 4 randomized controlled trials evaluating rFVIIa (recombinant factor VIIa) 80 μg/kg to placebo. METHODS: We generated polychotomous strata of HES using absolute growth thresholds (≤0/<6/≥6 mL) and quintiles of percent volume change. The relationship between treatment and HES was assessed using proportional odds models. Differences in subgroups based on baseline volume (≥ or <20 mL), and time from symptom onset to treatment (≤ or >2 hours) were explored with testing for interactions. RESULTS: The primary analysis included 721 patients. At 24 hours, 36% (134/369) of rFVIIa-treated patients exhibited no hematoma expansion as compared with 25% of placebo (88/352)-treated patients. Significant expansion (≥6 mL) was reduced by 10% in those treated with rFVIIa-(adjusted common odds ratio [acOR], 0.57 [95% CI, 0.43-0.75]). An examination of percent change similarly showed a shift across the spectrum of expansion (acOR, 0.61 [95% CI, 0.47-0.80]). In both groups, mild-to-moderate expansion was observed in 38% to 47% of patients, depending on the threshold used. Differences in absolute HES between the rFVIIa and placebo groups were more pronounced in patients with baseline hemorrhage volumes ≥20 mL (acOR, 0.48 [95% CI, 0.30-0.76] versus <20 mL: acOR, 0.67 [95% CI, 0.47-0.95]; =0.02). No treatment interaction in patients treated within 2 or after 2 hours from onset was observed (acOR, 0.42 [95% CI, 0.19-0.91 versus >2 hours: acOR, 0.59 [95% CI, 0.44-0.79]; =0.30). CONCLUSIONS: The association between rFVIIa and hematoma growth arrest is most pronounced in patients with larger baseline volumes but is evident across the full spectrum of treated patients.

Recommended Citation

Yogendrakumar, V., Mayer, S. A., Steiner, T., Broderick, J. P., & Dowlatshahi, D. (2023). Exploring Hematoma Expansion Shift With Recombinant Factor VIIa: A Pooled Analysis of 4 Randomized Controlled Trials. Stroke, 54 (12), 2990-2998. https://doi.org/https://doi.org/10.1161/STROKEAHA.123.043209